Inhibition of endogenous hydrogen sulfide synthesis by PAG protects against ethanol-induced gastric damage in the rat

Hydrogen sulfide (H₂S) is a gaseous mediator involved in a multitude of physiological functions; however the role of H₂S in the gut is far from being understood completely. The aim of this study was to determine the effect of d-l-propargylglycine (PAG), an inhibitor of H₂S synthesis, on ethanol-induced gastric injury in rat and to examine the role of l-cysteine, exogenous H₂S, prostaglandins, non-protein sulphydryls groups, nitric oxide and K_ATP channels in the gastroprotective effect of PAG. Administration of PAG (3.12 to 75mg/kg i.p.) or l-cysteine (0.3 to 300mg/kg, p.o.) exhibited a dose-dependent protective effect after intragastric administration of 1ml of ethanol to induce gastric injury. The gastroprotective effect of PAG (25mg/kg i.p.) was maintained after post-treatment with l-cysteine (10mg/kg p.o.), while NaHS (8.4mg/kg p.o.) inhibited this effect. The levels of gastric hydrogen sulfide were increased after ethanol-induced gastric damage and they were reverted by PAG while prostaglandin E₂ levels in gastric tissue were decreased by ethanol and PAG did not revert to this effect. Pretreatment with indomethacin (10mg/kg i.p.) and N-ethylmaleimide (NEM, 10mg/kg s.c.) resulted in a reversion of the gastroprotective effect of PAG while N^G-nitro-l-arginine methyl ester (L-NAME, 70mg/kg s.c.), glibenclamide (1mg/kg i.p.) or diazoxide (3mg/kg i.p.) did not induce any changes. These results suggest that ethanol-induced gastric injury is related with an increment of endogenous H₂S levels, and therefore a decrement of H₂S levels by PAG is a benefit to protect gastric injury caused by ethanol.